PROJECT SUMMARY We are requesting funds to purchase a PacBio Sequel long-read, single molecule sequencer, the latest next-generation sequencing instrument, released in September of 2015. The system will be placed in the Genome Technology Center (GTC) at New York University Langone Medical Center (NYULMC), a shared resource administered by the Office of Collaborative Science and operated by experienced and highly trained staff. The GTC is under the direction of Dr. Adriana Heguy, an expert in genomics with many years of experience providing genomics research in a collaborative setting. Currently the GTC provides only short read sequences on our three HiSeqs and two MiSeqs. We have no long read single molecule capability, with the exception of a MinION which has very limited throughput and capabilities, a high error rate and is not industry-standard. The requested PacBio Sequel will be utilized to fulfill the needs of a large community of NYU investigators with established and NIH funded research programs in microbiology, metagenomics, immunology, parasite biology and basic cellular processes such as DNA methylation and DNA repair, all of which require long-read, single molecule sequencing. These projects cannot be carried out with current short-read technology and their progress has been hampered by limited access to long-read sequencing through other institutions. The PacBio Sequel is the best instrument for the needs of our investigators; it provides increased capacity and flexibility, requires less space and operates at a lower cost as compared to the previous generation PacBio RS II System. The redesigned SMRT flow cell is based on their industry- standard, proven technology for long reads, high accuracy, uniform coverage and simultaneous epigenetic characterization. The PacBio Sequel will support the NIH funded projects of 7 Major Users and 6 Minor Users at NYU. The Major Users will occupy 68% of instrument capacity; 97% capacity for combined usage of both groups. All users are NIH funded. Any remaining capacity of this instrument will be allocated for pilot projects to generate preliminary data for grant proposals. We have extensive bioinformatics and high performance computing capabilities, already enabled for PacBio data analysis and storage. NYULMC is committed to supporting cutting edge genomics through strong institutional support of the GTC, and the acquisition, implementation and maintenance of the PacBio Sequel.